Perceptions of Chinese Biomedical Researchers Towards Academic Misconduct: A Comparison Between 2015 and 2010.

Publications by Chinese researchers in scientific journals have dramatically increased over the past decade; however, academic misconduct also becomes more prevalent in the country. The aim of this prospective study was to understand the perceptions of Chinese biomedical researchers towards academic misconduct and the trend from 2010 to 2015. A questionnaire comprising 10 questions was designed and then validated by ten biomedical researchers in China. In the years 2010 and 2015, respectively, the questionnaire was sent as a survey to biomedical researchers at teaching hospitals, universities, and medical institutes in mainland China. Data were analyzed by the Chi squared test, one-way analysis of variance with the Tukey post hoc test, or Spearman's rank correlation method, where appropriate. The overall response rates in 2010 and 2015 were 4.5% (446/9986) and 5.5% (832/15,127), respectively. Data from 15 participants in 2010 were invalid, and analysis was thus performed for 1263 participants. Among the participants, 54.7% thought that academic misconduct was serious-to-extremely serious, and 71.2% believed that the Chinese authorities paid no or little attention to the academic misconduct. Moreover, 70.2 and 65.2% of participants considered that the punishment for academic misconduct at the authority and institution levels, respectively, was not appropriate or severe enough. Inappropriate authorship and plagiarism were the most common forms of academic misconduct. The most important factor underlying academic misconduct was the academic assessment system, as judged by 50.7% of the participants. Participants estimated that 40.1% (39.8 ± 23.5% in 2010; 40.2 ± 24.5% in 2015) of published scientific articles were associated with some form of academic misconduct. Their perceptions towards academic misconduct had not significantly changed over the 5 years. Reform of the academic assessment system should be the fundamental approach to tackling this problem in China.

Epigallocatechin gallate inhibits HBV DNA synthesis in a viral replication - inducible cell line.

AIM: To analyze the antiviral mechanism of Epigallocatechin gallate (EGCG) against hepatitis B virus (HBV) replication. METHODS: In this research, the HBV-replicating cell line HepG2.117 was used to investigate the antiviral mechanism of EGCG. Cytotoxicity of EGCG was analyzed by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Hepatitis B virus e antigen (HBeAg) and hepatitis B virus surface antigen (HBsAg) in the supernatant were detected by enzyme-linked immunosorbent assay. Precore mRNA and pregenomic RNA (pgRNA) levels were determined by semi-quantitative reverse transcription polymerase chain reaction (PCR) assay. The effect of EGCG on HBV core promoter activity was measured by dual luciferase reporter assay. HBV covalently closed circular DNA and replicative intermediates of DNA were quantified by real-time PCR assay. RESULTS: When HepG2.117 cells were grown in the presence of EGCG, the expression of HBeAg was suppressed, however, the expression of HBsAg was not affected. HBV precore mRNA level was also down-regulated by EGCG, while the transcription of precore mRNA was not impaired. The synthesis of both HBV covalently closed circular DNA and replicative intermediates of DNA were reduced by EGCG treatment to a similar extent, however, HBV pgRNA transcripted from chromosome-integrated HBV genome was not affected by EGCG treatment, indicating that EGCG targets only replicative intermediates of DNA synthesis. CONCLUSION: In HepG2.117 cells, EGCG inhibits HBV replication by impairing HBV replicative intermediates of DNA synthesis and such inhibition results in reduced production of HBV covalently closed circular DNA.

HCV NS2 protein inhibits cell proliferation and induces cell cycle arrest in the S-phase in mammalian cells through down-regulation of cyclin A expression.

Chronic hepatitis C virus (HCV) infection often leads to liver cancer. NS2 protein is a HCV hydrophobic transmembrane protein that associates with several cellular proteins in mammalian cells. In this report, we investigated the functions of NS2 protein by examining its effects on cell growth and cell cycle progression. Stable NS2-expressing HeLa and Vero cell lines were established by transfection of the cells with pcDNA3.1(-)-NS2 followed by selection of the transfected cells in the presence of G418. We found that the proliferation rates of both NS2-expressing cell lines were inhibited by 40-50% compared with the control cells that were transfected with pcDNA3.1(-) control vector. Cell cycle analysis of these NS2-expressing cell lines shows that the proportion of cells in the S-phase increased significantly compared to that of control cells that do not express NS2 protein, suggesting NS2 protein induces cell cycle arrest in the S-phase. Further studies showed that the induction of cell cycle arrest in the S-phase by NS2 protein is associated with the decrease of cyclin A level. In contrast, the expression of NS2 protein does not affect the levels of cyclin-dependent kinase CDK2, CDK4, cyclin D1, or cyclin E. Our results suggest that HCV NS2 protein inhibits cell growth and induces the cell cycle arrest in the S-phase through down-regulation of cyclin A expression, which may be beneficial to HCV viral replication. Our findings not only provide information in the understanding mechanism of HCV infection, but also provide guidance for the future development of potential therapeutics for the prevention and treatment of the viral infection.

Activation of NF-kappaB by the full-length nucleocapsid protein of the SARS coronavirus.

The severe acute respiratory syndrome coronavirus (SARS-CoV) is the major causative agent for the worldwide outbreak of SARS in 2003. The mechanism by which SARS-CoV causes atypical pneumonia remains unclear. The nuclear factor kappa B (NF-kappaB) is a key transcription factor that activates numerous genes involved in cellular immune response and inflammation. Many studies have shown that NF-kappaB plays an important role in the pathogenesis of lung diseases. In this study, we investigated the possible regulatory interaction between the SARS-CoV nucleocapsid (N) protein and NF-kappaB by luciferase activity assay. Our results showed that the SARS-CoV N protein can significantly activate NF-kappaB only in Vero E6 cells, which are susceptible to SARS-CoV infection, but not in Vero or HeLa cells. This suggests that NF-kappaB activation is cell-specific. Furthermore, NF-kappaB activation in Vero E6 cells expressing the N protein is dose-dependent. Further experiments showed that there is more than one function domain in the N protein responsible for NF-kappaB activation. Our data indicated the possible role of the N protein in the pathogenesis of SARS.

Hepatitis C virus non-structural 5A protein can enhance full-length core protein-induced nuclear factor-kappaB activation.

AIM: To study the effects of hepatitis C virus (HCV) core and non-structural 5A (NS5A) proteins on nuclear factor-kappaB (NF-kappaB) activity for understanding their biological function on chronic hepatitis caused by HCV infection. METHODS: Luciferase assay was used to measure the activity of NF-kappaB in three different cell lines cotransfected with a series of deletion mutants of core protein alone or together with NS5A protein using pNF-kappaB-Luc as a reporter plasmid. Western blot and indirect immunofluorescence assays were used to confirm the expression of proteins and to detect their subcellular localization, respectively. Furthermore, Western blot was also used to detect the expression levels of NF-kappaB/p65, NF-kappaB/p50, and inhibitor kappaB-a (IkappaB-a). RESULTS: The wild-type core protein (C191) and its mutant segments (C173 and C158) could activate NF-kappaB in Huh7 cells only and activation caused by (C191) could be enhanced by NS5A protein. Moreover, the full-length core protein and its different deletion mutants alone or together with NS5A protein did not enhance the expression level of NF-kappaB. The NF-kappaB activity was augmented due to the dissociation of NF-kappaB-IkappaB complex and the degradation of IkappaB-a. CONCLUSION: NF-kappaB is the key transcription factor that can activate many genes that are involved in the cellular immune response and inflammation. Coexpression of the full-length core protein along with NS5A can enhance the NF-kappaB activation, and this activation may play a significant role in chronic liver diseases including hepatocellular carcinoma associated with HCV infection.